Isolation of a natural DNA virus of <i>Drosophila melanogaster</i>, and characterisation of host resistance and immune responses

<div><p><i>Drosophila melanogaster</i> has played a key role in our understanding of invertebrate immunity. However, both functional and evolutionary studies of host-virus interaction in <i>Drosophila</i> have been limited by a dearth of native virus isolates. In particular, despite a long history of virus research, DNA viruses of <i>D</i>. <i>melanogaster</i> have only recently been described, and none have been available for experimental study. Here we report the isolation and comprehensive characterisation of Kallithea virus, a large double-stranded DNA virus, and the first DNA virus to have been reported from wild populations of <i>D</i>. <i>melanogaster</i>. We find that Kallithea virus infection is costly for adult flies, reaching high titres in both sexes and disproportionately reducing survival in males, and movement and late fecundity in females. Using the <i>Drosophila</i> Genetic Reference Panel, we quantify host genetic variance for virus-induced mortality and viral titre and identify candidate host genes that may underlie this variation, including <i>Cdc42-interacting protein 4</i>. Using full transcriptome sequencing of infected males and females, we examine the transcriptional response of flies to Kallithea virus infection and describe differential regulation of virus-responsive genes. This work establishes Kallithea virus as a new tractable model to study the natural interaction between <i>D</i>. <i>melanogaster</i> and DNA viruses, and we hope it will serve as a basis for future studies of immune responses to DNA viruses in insects.</p></div

Cyanides and thiocyanates in a hospital toxicology laboratory

L'ion cyanure est un poison très violent, susceptible d'entraîner chez l'Homme la mort en quelques minutes. Dans l'organisme, sous l'action principale de deux enzymes, la thiosulfate sulfure transférase et la β mercaptopyruvate transsulfurase, il se transforme en ion thiocyanate (SCN-), éliminé par voie urinaire. La détermination du taux sanguin du cyanure est importante pour confirmer le diagnostic d'intoxication. Les différentes méthodes de dosage des cyanures et thiocyanates dans les milieux biologiques sont présentées, en insistant particulièrement sur leur praticabilité et leur sensibilité respectives.Cyanide is a highly toxic poison, able to very rapidly induce the death. Thiocyanate anion (SCN-) is a metabolic product of cyanide and cyano-containing organic substances, produced by two major enzymes : thiosulfate sulfure transferase and β mercaptopyruvate transsulfurase. Determinations of blood cyanide is important to confirm the diagnostic of intoxication. A survey of methods for the quantitative determination of cyanide and thiocyanate in biological matrices is presented. Particular attention is paid to the rapidity and to the sensitivity of the method

The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila

International audienc

Toxiques et analyses biologiques en toxicologie hospitalière

peer reviewe

Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.

Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes. Furthermore, these antibody phenotypes were not affected by changes in environmental factors such as the gut microbiota composition. Antigen-specific B cells following immunization had a marked difference in capability to class switch, resulting in perturbed IgG isotype antibody production. In vitro, a B-cell intrinsic defect in the regulation of class-switch recombination was identified in mice with low IgG antibody production. Whole genome sequencing identified polymorphisms associated with the magnitude of antibody produced, and we propose candidate genes that may regulate isotype class-switching capability. This study highlights that mice sourced from different vendors can have significantly altered humoral immune response profiles, and provides a resource to interrogate genetic regulators of antibody responsiveness. Together these results further our understanding of immune heterogeneity and suggest additional research on the genetic influences of adjuvanted vaccine strategies is warranted for enhancing vaccine efficacy